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Quantitative urine confirmatory testing for synthetic cannabinoids in randomly collected urine specimens
Authors:Marisol S. Castaneto  Karl B. Scheidweiler  Ariane Wohlfarth  Kevin L. Klette  Thomas M. Martin  Marilyn A. Huestis
Affiliation:1. Chemistry and Drug Metabolism, National Institute on Drug Abuse, NIH, Baltimore, MD, USA;2. Program in Toxicology, University of Maryland Baltimore, Baltimore, MD, USA;3. Drug Testing and Program Policy, Office of the Under Secretary of Defense (Personnel and Readiness), Personnel Risk Reduction, Washington, DC, USA
Abstract:Synthetic cannabinoid intake is an ongoing health issue worldwide, with new compounds continually emerging, making drug testing complex. Parent synthetic cannabinoids are rarely detected in urine, the most common matrix employed in workplace drug testing. Optimal identification of synthetic cannabinoid markers in authentic urine specimens and correlation of metabolite concentrations and toxicities would improve synthetic cannabinoid result interpretation. We screened 20 017 randomly collected US military urine specimens between July 2011 and June 2012 with a synthetic cannabinoid immunoassay yielding 1432 presumptive positive specimens. We analyzed all presumptive positive and 1069 negative specimens with our qualitative synthetic cannabinoid liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method, which confirmed 290 positive specimens. All 290 positive and 487 randomly selected negative specimens were quantified with the most comprehensive urine quantitative LC‐MS/MS method published to date; 290 specimens confirmed positive for 22 metabolites from 11 parent synthetic cannabinoids. The five most predominant metabolites were JWH‐018 pentanoic acid (93%), JWH‐N‐hydroxypentyl (84%), AM2201 N‐hydroxypentyl (69%), JWH‐073 butanoic acid (69%), and JWH‐122 N‐hydroxypentyl (45%) with 11.1 (0.1‐2,434), 5.1 (0.1‐1,239), 2.0 (0.1‐321), 1.1 (0.1‐48.6), and 1.1 (0.1‐250) µg/L median (range) concentrations, respectively. Alkyl hydroxy and carboxy metabolites provided suitable biomarkers for 11 parent synthetic cannabinoids; although hydroxyindoles were also observed. This is by far the largest data set of synthetic cannabinoid metabolites urine concentrations from randomly collected workplace drug testing specimens rather than acute intoxications or driving under the influence of drugs. These data improve the interpretation of synthetic cannabinoid urine test results and suggest suitable urine markers of synthetic cannabinoid intake. This article is a U.S. Government work and is in the public domain in the USA.
Keywords:synthetic cannabinoids  immunoassay  LC‐MS/MS  urine drug testing
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